AB1007 CLINICAL SIGNIFICANCE OF SERUM CREATININE-TO-CYSTATIN C RATIO AS A SURROGATE MARKER FOR INCIDENT OSTEOPOROTIC FRACTURE
Authors: I. Yoshii, N. Sawada, T. Chijiwa
Journal: Annals of the Rheumatic Diseases (2022)

Background In a previous article, we introduced a novel index of osteoporosis that represented as T-score ≤ -2.5, which constituted the combined criteria of age, serum creatinine-to-cystatin C ratio (Cr/CysC), and tartrate-resistant acid phosphatase-5b. Objectives We hypothesized that serum cystine C to creatine ratio (CysC/Cr), that is the reciprocal of Cr/CysC, might function as a predictive marker of incident osteoporotic fractures in elderly population and tested this hypothesis in a retrospective cohort study. Methods Subjects were 50 years of age or older who had their lumbar spine and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, and simultaneously had their CysC/Cr measured. The dates of BMD and CysC/Cr measurements were set as baseline. The primary outcomes were incidental major osteoporotic fractures (MOF), including vertebral fractures, proximal femur fractures, proximal humerus fractures, and distal radius fractures. Follow-up was continued until the first fracture occurred, was terminated at death, was lost to follow-up, or was completed. In these patients, the relationship between baseline developmental MOF and variants was investigated using Cox regression analysis. The variants were candidate risk factors for MOF for positivity and negativity. After identifying risk factors using univariate models, multivariate model was undergone in order to relative higher risk in the factors. Receivers operating characteristic analyses (ROC) were conducted in order to determine cut-off index (COI) of these factors. Kaplan-Meier survival analysis was tested in order to determine hazard ratio for presenting these risk factors. Results A total of 175 patients, 38 men and 137 women, were included in the dataset. The mean age at baseline was 70.2 years, ranged from 50 to 98 years, and the mean follow-up was 30.4 months. Mean BMD at baseline was 0.734 and 0.659 g/cm 2 (T-score: -2.21 and -2.04) in lumbar spine and femoral neck, respectively, and mean CysC/Cr at baseline was 1.49. fall-ability, LSD, and pr-MOF, were present in, 59, 113, and 77, respectively. Administration of OPD, vitamin-D, GCS, and polypharmacy were present in 92, 170, 12, and 47, respectively (Table 1). Table 1. Results of receiver operation characteristics and Kaplan-Meier survival analysis for each factor Factor cut-off index area under the curve p-value Hazard ratio (95%CI) p-value CysC/Cr &gt; 1.345 0.614 &lt; 0.01 6.32 (2.87 – 13.92) &lt; 0.01 LSD present 0.626 &lt; 0.01 3.60 (1.67 – 7.73) &lt; 0.05 Fall-ability present 0.703 &lt; 0.001 4.83 (2.16 – 10.21) &lt; 0.001 CKD present 0.612 &lt; 0.05 2.56 (1.06 – 6.20) &lt; 0.05 pr-MOF present 0.685 &lt; 0.001 4.81 (2.08 – 9.39) &lt; 0.001 In Cox regression analysis, the presence of prevalent MOF (pr-MOF), fall-ability, lifestyle-related diseases (LSD), chronic kidney diseases (CKD) ≥ Grade3a, and higher CysC/Cr had significant higher risk ratios with univariate models. In these, the presence of LSD and fall-ability had significant higher risk ratios with multivariate model. All the binary factors had COI as the presence of each event such with 0.626, 0.703, 0.612, and 0.685 of area under the curve for LSD, Fall-ability, CKD, and pr-MOF, respectively. CysC/Cr also had COI (1.345) with 0.614 of the area under the curve. In the Kaplan-Meier survival analysis, CysC/Cr &gt; COI, Fall-ability, pr-MOF, LSD, CKD ≥ Grade 3 b was significantly higher in descending order of Hazard ratio (6.32, 4.83, 4.81, 3.60, 2.56, respectively) (Table 1). Conclusion These results suggest that CysC/Cr may be a predictor of MOF or a risk factor if it exceeds the COI. This value is the reciprocal of Cr/CysC, and if Cr/CysC reflects muscle mass, CysC/Cr is assumed to reflect low relative muscle mass. It is supposed that this is also affected by sex difference and age. There seems to be a correlation between MOF and CysC/Cr. Early measurement of CysC/Cr facilitates screening for fractures. As a result, it may be easier to implement fracture prevention programs such as drug interventions such as OPD and exercise habit guidance. Disclosure of Interests None declared